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Dai Y, Zhang J: Chloride efflux is involved in ET-1 and 5-HT-induced contraction in rabbit basilar artery. J Cardiovasc Pharmacol. 2004 Nov;44 Suppl 1:S125-8.
Chloride (Cl-) efflux induces depolarization and contributes to contraction of cerebral arteries. We tested the effect of endothelin-1 and 5-hydroxytryptamine on isometric tension in rabbit basilar artery by inhibition of Na+-K+-2Cl- co-transporter and Cl-/HCO3- exchanger to decrease Cl-, by decreasing extracellular Cl- concentration, and by blocking Cl- channels using Cl- channel inhibitors. We have made the following observations: (i) endothelin-1 and 5-hydroxytryptamine produced contraction in the normal Cl- Krebs-Henseleit bicarbonate solution (123 mM Cl-); (ii) inhibition of Na+-K+-2Cl- co-transporter with bumetanide abolished the contractions; (iii) bicarbonate-free solution with HEPES reduced contractions to 5-hydroxytryptamine and endothelin-1; (iv) substitution of extracellular Cl- with methanesulfonate acid (MS- 113 mM, Cl- 10 mM) enhanced peak contraction to 5-hydroxytryptamine and endothelin-1 and decreased plateau contraction to 5-hydroxytryptamine, but did not affect the plateau contraction to endothelin-1 and KCl; and (v) blockade of Ca2+-dependent Cl- channel with niflumic acid and non-selective Cl- channel with 5-nitro-2-(3-phenylpropylamino) benzoic acid and indanyloxyacetic acid-94, R- (+)-methylindazone (R- (+)-IAA-94) decreased contractions to endothelin-1 and 5-hydroxytryptamine.However, removal of endothelium attenuated the effect of Cl-channel inhibitors. In conclusion, Cl- channels and Cl- flux are involved in endothelin-1-induced and 5-hydroxytryptamine-induced contraction in rabbit basilar artery. Cl- channel blockers might exert additional effects by releasing vasodilatation agents from endothelial cells. |
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